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带有胺基供体侧链的亚胺-酚盐配体新型铜(II)配合物的抗氧化和抗癌潜力

Antioxidant and Anticancer Potential of the New Cu(II) Complexes Bearing Imine-Phenolate Ligands with Pendant Amine N-Donor Groups.

作者信息

Pinheiro Adriana Castro, Nunes Ianka Jacondino, Ferreira Wesley Vieira, Tomasini Paula Pellenz, Trindade Cristiano, Martins Carolina Cristóvão, Wilhelm Ethel Antunes, Oliboni Robson da Silva, Netz Paulo Augusto, Stieler Rafael, Casagrande Osvaldo de Lazaro, Saffi Jenifer

机构信息

Laboratory of Genetic Toxicology, Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre 90050-170, RS, Brazil.

Group of Catalysis of Theoretical Studies, Center of Chemical, Pharmaceutical and Food Science Center, Federal University of Pelotas (UFPel), Pelotas 96160-000, RS, Brazil.

出版信息

Pharmaceutics. 2023 Jan 22;15(2):376. doi: 10.3390/pharmaceutics15020376.

Abstract

Cu(II) complexes bearing NNO-donor Schiff base ligands (, ) have been synthesized and characterized. The single crystal X-ray analysis of the complex revealed that a mononuclear and a dinuclear complex co-crystallize in the solid state. The electronic structures of the complexes are optimized by Density Functional Theory (DFT) calculations. The monomeric nature of and species is maintained in solution. Antioxidant activities of the ligands (, ) and Cu(II) complexes (, ) were determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS). Our results demonstrated that showed better antioxidant activity. MTT assays were performed to assess the toxicity of ligands and Cu(II) complexes in V79 cells. The antiproliferative activity of compounds was tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and SW620 (colorectal carcinoma) and on MRC-5 (normal lung fibroblast). All compounds showed high cytotoxicity in the all-cell lines but showed no selectivity for tumor cell lines. Antiproliferative activity by clonogenic assay showed a more significant inhibitory effect on the MCF-7 cell lines than on MRC-5. DNA damage for the compound at 10 µM concentration was about three times higher in MCF-7 cells than in MRC-5 cells.

摘要

已合成并表征了带有NNO供体席夫碱配体的铜(II)配合物(,)。对该配合物的单晶X射线分析表明,单核和双核配合物在固态中共结晶。通过密度泛函理论(DFT)计算优化了配合物的电子结构。和物种的单体性质在溶液中得以保持。通过体外试验如1,1-二苯基-2-苦基肼自由基(DPPH)和2,2'-偶氮双(3-乙基苯并噻唑啉-6-磺酸)自由基(ABTS)测定了配体(,)和铜(II)配合物(,)的抗氧化活性。我们的结果表明表现出更好的抗氧化活性。进行MTT试验以评估配体和铜(II)配合物在V79细胞中的毒性。测试了化合物对两种人类肿瘤细胞系的抗增殖活性:MCF-7(乳腺腺癌)和SW620(结肠直肠癌)以及MRC-5(正常肺成纤维细胞)。所有化合物在所有细胞系中均显示出高细胞毒性,但对肿瘤细胞系无选择性。通过克隆形成试验的抗增殖活性对MCF-7细胞系的抑制作用比对MRC-5更显著。在10μM浓度下,化合物对MCF-7细胞的DNA损伤比MRC-5细胞高约三倍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5235/9960331/1e1401dfd4d5/pharmaceutics-15-00376-sch001.jpg

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